Two AFS Members Receive the Rachel Carson Award for Scientific Excellence (Group)

Rachel Carson Award for Scientific Excellence (Group) – 2013 The U.S. Fish and Wildlife Service Aquatic Animal Drug Approval Partnership Program (AADAPP) Research Program generates high quality data to support fish drug approval, making safe and effective fish drugs available to Service and other fisheries professionals. AADAPP staff – James Bowker (AFS), Molly Bowman, Dan Carty (AFS), and Niccole Wandelear – are fish biologists with specialized skills and are leading experts in the country on conducting research and generating fish drug approvals in the United States.

The U. S. Fish and Wildlife Service (Service) Aquatic Animal Drug Approval Partnership Program (AADAPP) was established in 1994 to solve the crisis created when the U. S. Food and Drug Administration (FDA) began to enforce the Federal Food, Drug, and Cosmetic Act and FDA regulations regarding the use of drugs in Minor Species, including fish. This decision effectively stripped the National Fish Hatchery System (NFHS) of virtually all the tools that it had used for decades to manage fish health and achieve Service fish culture, fisheries management, and fisheries research objectives. AADAPP’s goal was to work within the newly enforced regulatory framework and put these essential tools back in the hands of Service personnel who needed them. The AADAPP Research Program (RP) generates high quality data to support fish drug approvals. Guiding safe and effective fish drugs ’through the approval pipeline” and into the hands of Service and other fisheries professionals is of the utmost importance because it makes accessing and using fish drugs simpler and also demonstrates the Service’s good faith and commitment to the drug approval effort. Obtaining FDA approval for use of a drug on food animals, including fish, is a long, arduous, and expensive process (e.g., $10-20M and 15-30 years). The FDA approval process that AADAPP follows has become the ”gold standard” throughout the world because of its rigorous approach to protecting the public and preventing unsafe or ineffective drugs from reaching the marketplace. The RP has taken lead responsibility to establish safe and effective treatment regimens for many drugs that have been approved by FDA. Over time, AADAPP researchers have developed expertise in regulatory science and the ability to conduct research in compliance with Good Clinical Practices and Good Laboratory Practice (GLP) requirements. In terms of the quality of its work, AADAPP is considered by FDA to be “on par with major pharmaceutical companies”. AADAPP researchers, understanding the broader implications of their work and their obligations as scientists, strive to develop experimental designs that fulfill regulatory requirements established by FDA and to provide beneficial information to fellow researchers and fisheries professionals. To date, AADAPP researchers have authored or co-authored (1) more than 20 peer-reviewed publications on the safety and effectiveness of a variety of fish drugs, including sedatives and antimicrobials; (2) an American Fisheries Society Policy Statement on the Need for an Immediate-Release Anesthetic/Sedative for Use in the Fisheries Disciplines, and (3) a Guide to Using Drugs, Biologics, and other Chemicals in Aquaculture. At present, the AADAPP program is the only program in the country singularly committed to conducting research and generating data to support fish drug approvals in the United States, and the AADAPP staff is considered some of the leading experts in the country on this subject. AADAPP research staff members are Jim Bowker, Dan Carty, Molly Bowman, and Niccole Wandelear. All research staff are fish biologists with specialized skills in experimental design, data collection and analysis, conducting studies in compliance with GLP requirements, conducting research within a strict regulatory framework where results are of interest to fisheries professionals, working effectively with each other and partners, and technical writing, and are therefore nominated as a group for the Rachel Carson Award for Scientific Expertise.

Award Criteria 2: Scientific Contribution

During the period 2009-2013, AADAPP researchers worked collaboratively with federal, state, and academic institution partners to conduct studies to support approval of three fish drugs.

AQUAFLOR – Studies were conducted to evaluate the effectiveness of this antibiotic to control mortality in largemouth bass and bluegill caused by columnaris disease associated with Flavobacterium columnare, and on sunshine bass and yellow perch to determine safety.

SLICE – Studies were conducted to evaluate the effectiveness of this parasiticide administered to control infestations of Salmincola californiensis in adult rainbow trout, and on rainbow trout to determine safety.

AQUI-S20E – Fifteen studies were conducted to evaluate the effectiveness of this drug to sedate a variety of freshwater finfish to handleable within 2-3 min. Safety studies were conducted to establish the margin of safety for this sedative on representative freshwater finfish.

Each of these studies required a unique experimental design and innovative data analysis. Detailed reports ranging in length from 200 – 1200 pages were submitted to FDA for review and acceptance, and all reviewed reports have been. Conducting and reporting research so that it is acceptable by FDA involves a degree of rigor that is commonplace in human medicine and drug research trials but that is virtually nonexistent in fisheries research. Although this is AADAPP’s primary purpose, researchers go above and beyond the call of duty, disseminating their work to the broader community of fisheries professionals and scientists, summarizing study results in in-house publications and manuscripts in peer-reviewed journals:

The AADAPP produces large volumes of deliverables—FDA-accepted data and study reports, bulletins, publications, and presentations to fisheries professionals and the lay public. However, the true application and scientific value of their work is not in these short-term deliverables—though these are certainly many and individually meritorious—but in the long-term impacts of the program: putting needed tools in the hands of fisheries professionals. Because of the lengthy and difficult process to gain a drug approval, there are currently only eight drugs approved by FDA for use on at least some fish for at least one claim, and approvals of new drugs or new claims for drugs currently approved are infrequent (once every 4-5 years). Because of AADAPP’s contributions, the following claims were approved by FDA in April 2012 to allow use of AQUAFLOR to control mortality in all freshwater (1) fish due to columnaris disease and (2) warmwater finfish due to streptococcal septicemia. These are landmark successes because columnaris disease and streptococcal septicemia affect many cultured fish in the United States, and there was previously no drug approved for such broad use. Approval for the three new claims provides fisheries professionals and veterinarians involved in fish culture with much needed tools to produce healthy fish that will support further a healthy environment and human population. SLICE is an extremely important drug because it is essential for controlling parasitic infestations in valuable

broodstock or imperiled fish species. The studies conducted by AADAPP researchers to evaluate the safety and effectiveness of SLICE to control infestations of Salmincola californiensis were accepted by FDA and were deemed sufficient to complete all safety and effectiveness data requirements to support an approval for this product. Whereas much of the AADAPP research team efforts are focused on generating data to support approvals of therapeutants where use will be restricted to hatcheries, research conducted on other drugs, including fish sedatives, has been conducted to help facilitate traditional field biology and fisheries management. The studies conducted by AADAPP researchers to demonstrate the effectiveness of AQUI-S20E to sedate freshwater fish to handleable have been accepted by FDA. Safety studies have been completed and submitted to FDA for review. Results from the safety studies have shown that fish can be exposed to doses much higher and for durations much longer than that needed to sedate fish to handleable, thus establishing predetermined margins of safety.

Award Criteria 3: Extraordinary Results

In addition to generating sound scientific data that has contributed greatly to the fields of fish culture and fish health, results on AQUAFLOR have been used by the drug’s sponsor to obtain approval for additional uses. Legal and judicious use of this drug to control mortality caused by certain diseases has provided fisheries managers with healthier stocks of fish to enhance recreational fishing opportunities or for restoration/conservation efforts. Fish stocking efforts and the economics associated with fisheries and aquaculture in the United States have been well established (e.g., Halverson 2008, Stocking Trends: A Quantitative Review of Governmental Fish Stocking in the United States, 1931 to 2004; USFWS 2011, The Economic Value of Fisheries Conservation). Although it is difficult to confirm, it has been estimated that 2-5% of fish reared in North America are treated with drugs at some point during their time in a hatchery. It has been estimated that 20% of fish in a population of sick fish treated with a fish drug did not die because of the disease. Whether or not these estimates could be more accurate, it is clear that AADAPP research has resulted in fish drug approvals resulting in substantial contributions to maximizing the number of stocked fish and the associated economic value. For example, Halverson (2008) reported that 1.7 billion fish were produced in 2004 for stocking by the Service and state partners. Using the estimates above, legal and judicious use of fish drugs saved approximately 12M fish. To put this in perspective, that’s twice the number of fish stocked by the Service in 2004. In the Fisheries Economics of the United States, NOAA reported that in 2011 nearly 1billion lbs of Pacific salmon, with an estimated value of $618M, were caught. It is estimated that 50% of the Pacific salmon caught off the coast of Alaska and 80% caught off the coast of Washington are fish of hatchery origin. Based on these new approvals, fisheries professionals have an effective treatment option to control mortality in populations of salmon diagnosed with certain diseases. As fish stocking efforts in the U. S. increase, the impact of AADAPP research that has contributed to fish drug approvals will increase. Ongoing efforts to gain an initial approval of AQUI-S20E as a fish sedative has resulted in an increased awareness that it is the only legal option available to fisheries professionals and researchers if treated fish are to be released back into the environment immediately or shortly after sedation. Due to AADAPP’s contribution, it is anticipated that there will be an initial approval for this drug in 2015 as an immediate-release sedative.

The Service’s NFHS fish stocking efforts have had considerable economic and social impact in the U.S., depending on whether stocking efforts were for recreational fishing or for recovery of imperiled fish species. Fisheries management in the U.S. is science-based and in many cases requires tools like marking agents, fish sedatives, and spawning aids. AADAPP contributions listed above reflect just an example of the research team’s contribution and are consistent with past accomplishments. The AADAPP staff is involved in the development of the right tools for treating sick or infested fish, sedating fish, marking skeletal tissue of fish, or for facilitating spawning efforts that support essential activities of the NFHS, the Service, and the Service’s many partners involved in aquatic resource conservatio